TY - JOUR T1 - Evidence for the activity of lamotrigine at 5-HT<sub>1A</sub> receptors in the mouse forced swimming test JF - Journal of Psychiatry and Neuroscience JO - JPN SP - 275 LP - 282 VL - 30 IS - 4 AU - Michel Bourin AU - Fabienne Masse AU - Martine Hascoët Y1 - 2005/07/01 UR - http://jpn.ca/content/30/4/275.abstract N2 - Background: The antiepileptic drug lamotrigine is effective in the treatment of focal epilepsies. It is thought to act by inhibition of glutamate release through blockade of voltage-sensitive sodium channels and stabilization of the neuronal membrane. Lamotrigine is also effective in the treatment of mood disorders such as bipolar disorder. However, its exact mechanism of action in these conditions remains unclear. The aim of the present study was to evaluate the antidepressant-like effect of lamotrigine in a mouse model of depression, namely the forced swimming test (FST). Association studies using specific and nonspecific ligands acting on serotonin (5-hydroxytryptamine; 5-HT1) receptor subtypes were undertaken to evaluate the potential role of these receptors in the anti-immobility effect of lamotrigine.Methods: The mouse FST was performed after single administration of lamotrigine. Subactive doses of lamotrigine were administered in association with subactive doses of the following 5-HT1 receptor agonists or antagonists: 8-hydroxy-2-(di- n-propilamino)-tetralin (8-OH-DPAT, a standard 5-HT1A receptor selective agonist), pindolol (a presynaptic and postsynaptic 5-HT1A/1B receptor antagonist), NAN-190 (a 5-HT1A receptor antagonist), RU 24969 (a 5-HT1A/1B receptor agonist) and anpirtoline (5-HT1B agonist).Results: Lamotrigine impaired spontaneous locomotor activity at doses of 4 mg/kg or greater, and activity decreased by more than 50% at the 16 mg/kg dose. When administered alone, lamotrigine (8 and 16 mg/kg) decreased immobility time in the FST. Only 8-OH-DPAT (1 mg/kg), pindolol (32 mg/kg) and RU 24969 (0.5 mg/kg) enhanced the antidepressant-like effect of lamotrigine in the FST.Conclusions: These results suggest that postsynaptic 5-HT1A receptors might be involved in the activity of lamotrigine. Furthermore, they demonstrate that lamotrigine more closely resembles valproate and carbamazepine than lithium, with the advantage of an anti-immobility effect in the mouse FST when administered on its own. ER -